The FDA Says It’s More Compassionate Than You Think

Even as drug makers and desperate patients increasingly battle over access to experimental medicines for life-threatening conditions, Food and Drug Administration officials argue the agency is doing its part to make things right.

In the wake of some recent high-profile cases that made television news and prompted social media outcries, the FDA has released data showing that nearly every request it gets for “compassionate use”’ is approved.

The term refers to an FDA program in which individuals who are seriously sick and lack options are able to gain access to a medicine being developed, even though they are not enrolled in a clinical trial. For this to happen, a patient’s physician must first receive permission from the drug maker testing the medicine. From there, the physician must seek what amounts to a blessing from the FDA.

In recent years, the FDA has been very agreeable. In the fiscal year ended last October, the agency approved 863 requests, or 99 percent of all cases reviewed, according to FDA data. And one-third of those were approved on an emergency basis. In fact, the agency has approved 99 percent of all requests since October 2009. On average, 932 requests were endorsed annually since then.

“I think the numbers speak well for the program,” says Richard Klein, director of the patient liaison program in the FDA Office of Health and Constituent Affairs.

In reality, though, the process is not working as some patients would hope. Drug makers sometimes deny requests for compassionate use because they want to stick with strict trial criteria needed to win FDA marketing approval for their medicines. An unexpected patient reaction, for instance, might jeopardize a drug’s chance of success. In some instances, a company claims not to have sufficient supplies to handle a large number of requests.

This is what happened recently when a small biotech company called Chimerix denied a Virginia family. Their 7-year-old son, a cancer survivor, developed a viral infection after a bone marrow transplant and they hoped he would benefit from an antiviral drug Chimerix is developing. But repeated rejections became a publicity debacle as criticism was directed at the company and the FDA program as well.

The FDA said it intervened by working with Chimerix to design a pilot study to include the boy. That pilot study is now underway, according to a Chimerix spokesman. But an FDA spokeswoman says this was not the first time the FDA took such a step. Meanwhile, the FDA’s Klein says the agency is developing a new draft guidance, or blueprint, for handling expanded access cases.

“The agency only provides the pathway,” he says. “If a company is not willing to entertain a request [for compassionate use], then it doesn’t come to us. Most of the time, we only know about the applications where companies are willing to make drugs available. The numbers we have don’t include the times when companies say no. And there’s not a lot of data to say what the outcomes of these situations are.”

Maybe not. But perhaps FDA officials should find a way to require drug makers to report their compassionate use decisions – approvals and rejections – so the public can see the extent to which the program is having its intended effect.

Comments (4 of 4)

Mr. Walker's comment seems to suggest a paradigm where no one would want to participate in clinical trials, because they'd be able to get what they believe to be an effective option without doing so. And then, how would "We the People" ever know what therapies really worked and which didn't? I think back to the years of bone marrow transplant suffered by women with metastatic breast cancer simply because it became the standard of care, without real examination of just how effective it really was. Who would want to take a chance NOT using the standard of care? So, it was all but impossible to recruit people into research that would ultimately prove no survival benefit to the horrific treatment that brought women to the verge of death with high dose chemotherapy before attempting to reconstitute their bone marrow. I don't know exactly what the numbers are, but I've read that only a very small percentage of drugs that go into clinical trials ever make it to the "approved drug" side of the equation. Something like 80% fall off because they are too toxic, ineffective, or both. As I understand it, the current process is dependent on whether drug makers are willing to make their test drug available to patients outside of the clinical trial. Mr. Walker makes it sound as if the only difference between those who get an experimental drug and those who don't is whether they are in the trial - as if it's the one and only variable. But if I were in the drug business, I don't think I would make enough drug to supply everyone who might want it until I knew it was a home-run product. Otherwise, I'd be stuck with a lot of inventory if it was a bust. Not to mention the fact that if the drug had long term negative effects, I'd be all over TV in ads for those attorneys looking for anyone they could find who was injured in any way by a drug. Even if it was FDA-approved. Can only imagine if it wasn't!

8:31 am May 6, 2014

Steve Walker wrote:

Unfortunately, we continue to get misleading information from FDA on how well their access programs work. While FDA does approve most of the requests they ultimately get, the very small number of requests they actually receive is severely limited by their policies and interactions with the drug companies behind the scenes. The bottom line on FDA's access programs is that FDA administers them in ways that prevent them from working for all but a tiny minority of patients. In nearly every case, patients seeking access have a very serious or terminal disease, no approved medical options, and can't gain access to any potentially effective experimental drug in a clinical trial. They nearly always have the support of qualified physicians who think gaining access is their best medical option. Yet, the FDA's programs almost never work, by FDA intent. The FDA is well aware that its programs do not work, and has done nothing to materially improve them since they were first created in the 1980s. This is a major public health tragedy, made worse by FDA's (and Mr. Klein's) deflective reports that most of the tiny number of applications they receive are approved, when they also know that FDA is the reason so few patients ever manage to jump through all the hoops required to file an application in the first place. After more than a decade of trying to get the FDA to improve these programs, we have become convinced that the only way to make them work better is to remove FDA's authority to prevent access when a seriously- or terminally-ill patient has run out of all other options and, under the care of a qualified physician, chooses to be treated with an experimental drug that has already been shown in Phase I trials to be safe enough to be administered to many patients in larger, later phase trials for which the seeking patient is not eligible. The kind of access the Abigail Alliance has been calling for since 2001 has never proposed “unfettered access” to anything. All of our proposals, including our lawsuit and our legislative proposals have been designed to allow responsible access to drugs already being administered to patients in FDA-approved and supervised clinical trials. Further, patients almost universally seek access to highly promising drugs that have already shown substantial evidence of safety and effectiveness in ongoing clinical trials, and their only material difference from those receiving the drugs in clinical trials, is that they weren’t eligible for the trial – which is generally the case for most patients with a serious or terminal disease. The trials FDA wants aren’t big enough, nor do they allow enrollment of a broad enough set of patients with a given disease to serve more than a small fraction of patients who would participate if they could. The FDA trial requirements takes many years, and sometimes more than a decade, to complete. These experimental drugs would be prescribed and administered by qualified physicians, and patients would be monitored and cared for by those same physicians. We have also proposed in nearly all of our efforts to improve the system that we should be learning from administration of these drugs to patients outside the FDA’s sanctioned trials, and have included provisions that would make that a reality. With great respect for Peter Pitts, with whom we at the Abigail Alliance mostly agree, our experiences, and the experiences of many thousands of patients and families over the last 14 years in trying to work with FDA on this problem, has made it clear that absent legislation forcing FDA to make access work, it will not happen. FDA’s culture and regulatory science are stuck in 1962 when its authority to regulate the effectiveness of drugs, and the trial designs it would use to do that, were placed into its authorizing statutes by Congress. FDA has not moved from that point in time, and still points to events of that time or earlier (bear in mind that FDA is talking about events that happened more than 50 years ago) as justification for why it cannot and will not change the way it regulates today. It is time for a top to bottom overhaul of the FDA by Congress, and allowing and facilitating access to investigational drugs for patients who will otherwise just die waiting, for no defensible medical, societal or regulatory purpose, should be front and center in that overhaul.
Steven Walker, Co-Founder, Abigail Alliance

4:52 pm May 5, 2014

Peter Pitts wrote:

In January 2008, the U.S. Supreme Court, without comment, opted not to accept an appeal of Abigail Alliance v. von Eschenbach. In other words, the federal appeals court ruling that patients do not have a constitutional right to experimental drugs stands.

This is a tough, emotional issue and, with such heated rhetoric on both sides, it's easy to lose sight of the fact that everyone wants the same thing -- expanded access to drugs under clinical investigation.
For me this issue began (when I was Associate Commissioner for External Affairs at the FDA) during a meeting with Frank Burroughs (founder of the Abigail Alliance for Better Access to Developmental Drugs) and Terry Toigo (then the director of the FDA’s Office of Special Health Issues). The meeting centered on Frank’s assertion that the FDA could do more to expand its parameters for patient access. We all agreed more could be done. Frank left. Terry stayed – and I asked her why we (the FDA) used the term “compassionate use.” Her answer was simple – “It’s what we’ve always called it.”

I said, “Let’s change what we call it." Allowing desperately ill patients into clinical trial programs shouldn't be an act of noblesse oblige it should be an act of civil society. We decided to work towards changing the term to “expanded access.” And we did. It’s one of the things I am most proud of accomplishing during my time at the FDA.

But it has to be more than rhetoric. The words have to mean something – and what they have to mean is that more patients get more access to more experimental medicines more expeditiously. In many cases it is, literally, a life-or-death situation.

When it comes to pharmaceutical safety, pure libertarianism isn't in the best interests of the public health. Expanded access to experimental drugs simply can't and shouldn't morph into total, unfettered access.

That doesn't mean the status quo is working. What it means is that the FDA needs to figure out a way to dramatically broaden and facilitate expanded access to experimental drugs under its review. And the Abigail Alliance and its supporters need to keep up the pressure to improve the current system.

This is best done in a spirit of collegiality rather than a confrontational courtroom or in Congress. Should expanded access design and development planning discussions be binary conversations between a sponsor and the FDA? What about the patient community? Perhaps, as part of the FDA’s current initiatives to enhance both the timeliness and weight of the patient voice, expanded access plan development and execution should involve patient organizations.

it’s time to harness that power to make the process both more inclusive and better.

4:51 pm May 5, 2014

Peter Pitts wrote:

In January 2008, the U.S. Supreme Court, without comment, opted not to accept an appeal of Abigail Alliance v. von Eschenbach. In other words, the federal appeals court ruling that patients do not have a constitutional right to experimental drugs stands.

This is a tough, emotional issue and, with such heated rhetoric on both sides, it's easy to lose sight of the fact that everyone wants the same thing -- expanded access to drugs under clinical investigation.

For me this issue began (when I was Associate Commissioner for External Affairs at the FDA) during a meeting with Frank Burroughs (founder of the Abigail Alliance for Better Access to Developmental Drugs) and Terry Toigo (then the director of the FDA’s Office of Special Health Issues). The meeting centered on Frank’s assertion that the FDA could do more to expand its parameters for patient access. We all agreed more could be done. Frank left. Terry stayed – and I asked her why we (the FDA) used the term “compassionate use.” Her answer was simple – “It’s what we’ve always called it.”

I said, “Let’s change what we call it." Allowing desperately ill patients into clinical trial programs shouldn't be an act of noblesse oblige it should be an act of civil society. We decided to work towards changing the term to “expanded access.” And we did. It’s one of the things I am most proud of accomplishing during my time at the FDA.

But it has to be more than rhetoric. The words have to mean something – and what they have to mean is that more patients get more access to more experimental medicines more expeditiously. In many cases it is, literally, a life-or-death situation.

When it comes to pharmaceutical safety, pure libertarianism isn't in the best interests of the public health. Expanded access to experimental drugs simply can't and shouldn't morph into total, unfettered access.

That doesn't mean the status quo is working. What it means is that the FDA needs to figure out a way to dramatically broaden and facilitate expanded access to experimental drugs under its review. And the Abigail Alliance and its supporters need to keep up the pressure to improve the current system.

This is best done in a spirit of collegiality rather than a confrontational courtroom or in Congress. Should expanded access design and development planning discussions be binary conversations between a sponsor and the FDA? What about the patient community? Perhaps, as part of the FDA’s current initiatives to enhance both the timeliness and weight of the patient voice, expanded access plan development and execution should involve patient organizations.

it’s time to harness that power to make the process both more inclusive and better.